Comprehensive Physiology Wiley Online Library

Reproductive Hormone Influences on Thermoregulation in Women

Full Article on Wiley Online Library



Abstract

The present discussion reviews current knowledge regarding influences of the primary reproductive hormones on mechanisms of thermoregulatory control in women. The human body is remarkably capable of maintaining body temperature within a few tenths of a degree of normal (37°C) over a wide range of activity and environmental exposures; this regulation is accomplished via integration of central and peripheral thermal information at the preoptic area of the anterior hypothalamus (PO/AH). We describe both central and peripheral mechanisms involved in controlling thermoregulation in humans, and how these mechanisms are affected by sex and hormone exposure. Estrogens generally promote vasodilation, heat dissipation, and lower body temperature and progesterone or progestins generally have the opposite effect. Estrogens and progesterone/progestins can also interact with androgens; this is an important point because androgens in the body can increase in both older and younger women. The study of reproductive hormone (estrogens, progesterone, luteinizing, and follicle stimulating hormones) effects on body systems is challenging because of the complex and multifaceted influences of these hormones, both individually and in combination. Thus, a number of methods to alter hormone exposure are explained in this article. We conclude that men and women do not exhibit major quantitative differences in physiological thermoregulatory responses to exercise and/or body heating when factors such as fitness and body size are taken into account. However, female and male reproductive hormones have important influences that can significantly alter individual thermoregulatory responses at various points throughout the lifespan. © 2014 American Physiological Society. Compr Physiol 4:793‐804, 2014.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images


Figure 1. Figure 1. Schematic example of graphs used in analysis of thermoregulatory effector mechanisms (primarily sweating and cutaneous vasodilation), showing the relevant effector as a function of core body temperature. As core temperature increases, a point is reached (the threshold) at which the heat dissipation mechanism begins to increase. The slope of the relationship after this threshold is referred to as the sensitivity of the response. A “rightward” shift in threshold and/or a decrease in sensitivity will decrease the amount of heat dissipation for a given core temperature, resulting in less efficient heat loss. Vertical lines show the change in the amount of a given effector response (at a given core temperature) caused by a shift in threshold or sensitivity.
Figure 2. Figure 2. Typical concentrations of plasma estradiol and progesterone over a normal menstrual cycle (top) and during treatment with gonadotropin‐releasing hormone (GnRH) antagonist, followed by estradiol and progesterone (bottom). () With permission.
Figure 3. Figure 3. A classic example showing sweating rate as a function of esophageal temperature during the early follicular and mid luteal phases of the menstrual cycle. Note the shift to higher body core temperature of the sweating response in the luteal phase, resulting in lower sweating (and, presumably, heat dissipation) for a given core temperature in this phase (). With permission.
Figure 4. Figure 4. Data from Silva and Boulant () showing the response of a warm sensitive neuron in the rat PO/AH region to estradiol and testosterone perfusion. This particular neuron increased its activity in response to estradiol but not to testosterone. Overall, 26% of warm sensitive neurons studied increased activity in response to estradiol, and 32% increased activity in response to testosterone. With permission.
Figure 5. Figure 5. Sweating rate as a function of core temperature in women under three different hormone conditions. Women were studied while taking GnRH antagonist with estradiol (E2) (open circles), and while taking GnRH (open triangles) antagonist with estradiol + testosterone (E2 + T) (solid squares). Data are expressed as mean ± SEM. () With Permission.


Figure 1. Schematic example of graphs used in analysis of thermoregulatory effector mechanisms (primarily sweating and cutaneous vasodilation), showing the relevant effector as a function of core body temperature. As core temperature increases, a point is reached (the threshold) at which the heat dissipation mechanism begins to increase. The slope of the relationship after this threshold is referred to as the sensitivity of the response. A “rightward” shift in threshold and/or a decrease in sensitivity will decrease the amount of heat dissipation for a given core temperature, resulting in less efficient heat loss. Vertical lines show the change in the amount of a given effector response (at a given core temperature) caused by a shift in threshold or sensitivity.


Figure 2. Typical concentrations of plasma estradiol and progesterone over a normal menstrual cycle (top) and during treatment with gonadotropin‐releasing hormone (GnRH) antagonist, followed by estradiol and progesterone (bottom). () With permission.


Figure 3. A classic example showing sweating rate as a function of esophageal temperature during the early follicular and mid luteal phases of the menstrual cycle. Note the shift to higher body core temperature of the sweating response in the luteal phase, resulting in lower sweating (and, presumably, heat dissipation) for a given core temperature in this phase (). With permission.


Figure 4. Data from Silva and Boulant () showing the response of a warm sensitive neuron in the rat PO/AH region to estradiol and testosterone perfusion. This particular neuron increased its activity in response to estradiol but not to testosterone. Overall, 26% of warm sensitive neurons studied increased activity in response to estradiol, and 32% increased activity in response to testosterone. With permission.


Figure 5. Sweating rate as a function of core temperature in women under three different hormone conditions. Women were studied while taking GnRH antagonist with estradiol (E2) (open circles), and while taking GnRH (open triangles) antagonist with estradiol + testosterone (E2 + T) (solid squares). Data are expressed as mean ± SEM. () With Permission.
References
 1.NIH Policy and Guidelines on The Inclusion of Women and Minorities as Subjects in Clinical Research – October, 2001, 2001.
 2. Boulant JA . Neuronal basis of Hammel's model for set‐point thermoregulation. J Appl Physiol 100: 1347‐1354, 2006.
 3. Brooks‐Asplund EM , Cannon JG , Kenney WL . Influence of hormone replacement therapy and aspirin on temperature regulation in postmenopausal women. Am J Physiol Regulatory Integrative Comp. Physiol. 279: R839‐R848, 2000.
 4. Brooks‐Asplund EM , Kenney WL . Chronic hormone replacement therapy does not alter resting or maximal skin blood flow. J Appl Physiol 85: 505‐510, 1998.
 5. Brouha L , Smith PE, Jr , De Lanne R , Maxfield ME . Physiological reactions of men and women during muscular activity and recovery in various environments. J Appl Physiol 16: 133‐140, 1961.
 6. Burger HG , Dudley EC , Cui J , Dennerstein L , Hopper JL . A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone‐binding globulin levels through the menopause transition. J Clin Endocrinol Metab 85: 2832‐2838, 2000.
 7. Chang RT , Lambert GP , Moseley PL , Chapler FK , Gisolfi CV . Effect of estrogen supplementation on exercise thermoregulation on premenopausal women. J Appl Physiol 85: 2082‐2088, 1998.
 8. Charkoudian N . Mechanisms and modifiers of reflex induced cutaneous vasodilation and vasoconstriction in humans. J Appl Physiol 109: 1221‐1228, 2010.
 9. Charkoudian N , Johnson J . Altered reflex control of cutaneous circulation by female sex steroids is independent of prostaglandins. Am J Physiol 276 (Heart Circ Physiol. 45): H1634‐H1640, 1999.
 10. Charkoudian N , Johnson JM . Modification of active cutaneous vasodilation by oral contraceptive hormones. J Appl Physiol 83: 2012‐2018, 1997.
 11. Charkoudian N , Johnson JM . Reflex control of cutaneous vasoconstrictor system is reset by exogenous female reproductive hormones. J Appl Physiol 87: 381‐385, 1999.
 12. Charkoudian N , Stephens DP , Pirkle KC , Kosiba WA , Johnson JM . Influence of female reproductive hormones on local thermal control of skin blood flow. J Appl Physiol 87: 1719‐1723, 1999.
 13. Cheuvront SN , Haymes EM . Ad libitum fluid intakes and thermoregulatory responses of female distance runners in three environments. J Sports Sci 19: 845‐854, 2001.
 14. Deecher DC , Dorries K . Understanding the pathophysiology of vasomotor symptoms (hot flushes and night sweats) that occur in perimenopause, menopause, and postmenopause life stages. Archives of Women's Mental Health 10: 247‐257, 2007.
 15. Diotel N , Servili A , Gueguen M‐M , Mironov S , Pellegrini E , Vaillant C , Zhu Y , Kah O , Anglade I . Nuclear progesterone receptors are up‐regulated by estrogens in neurons and radial glial progenitors in the brain of zebrafish. PloS One 6: e28375, 2011.
 16. El‐Mas MM , Afify EA , Mohy El‐Din MM , Omar AG , Sharabi FM . Testosterone facilitates the baroreceptor control of reflex bradycardia: Role of cardiac sympathetic and parasympathetic components. J Cardiovascular Pharmacol 38: 754‐763, 2001.
 17. El‐Mas MM , Afify EA , Omar AG , Sharabi FM . Cyclosporine adversely affects baroreflexes via inhibition of testosterone modulation of cardiac vagal control. J Pharmacol Exp Ther 301: 346‐354, 2002.
 18. Elliot DL , Cheong J , Moe EL , Goldberg L . Cross‐sectional study of female students reporting anabolic steroid use. Arch Pediatr Adolesc Med 161: 572‐577, 2007.
 19. English JL , Jacobs LO , Green G , Andrews TC . Effect of the menstrual cycle on endothelium‐dependent vasodilation of the brachial artery in normal young women. Am J Cardiology 82: 256‐258, 1998.
 20. Fortney SM , Senay LC, Jr . Effect of training and heat acclimation on exercise responses of sedentary females. J Appl Physiol 47: 978‐984, 1979.
 21. Fox RH , Lofstedt BE , Woodward PM , Eriksson E , Werkstrom B . Comparison of thermoregulatory function in men and women. J Appl Physiol 26: 444‐453, 1969.
 22. Gagnon D , Crandall CG , Kenny GP . Sex differences in postsynaptic sweating and cutaneous vasodilation. J Appl Physiol 114: 394‐401, 2013.
 23. Gagnon D , Ganio MS , Lucas RA , Pearson J , Crandall CG , Kenny GP . Modified iodine‐paper technique for the standardized determination of sweat gland activation. J Appl Physiol 112: 1419‐1425, 2012.
 24. Gagnon D , Kenny GP . Does sex have an independent effect on thermoeffector responses during exercise in the heat? J Physiol 590: 5963‐5973, 2012.
 25. Gagnon D , Kenny GP . Sex differences in thermoeffector responses during exercise at fixed requirements for heat loss. J Appl Physiol 113: 746‐757, 2012.
 26. Gagnon D , Kenny GP . Sex modulates whole‐body sudomotor thermosensitivity during exercise. J Physiol 589: 6205‐6217, 2011.
 27. Götmar A , Hammar M , Fredrikson M , Samsioe G , Nerbrand C , Lidfeldt J , Spetz A‐C . Symptoms in peri‐ and postmenopausal women in relation to testosterone concentrations: data from The Women's Health in the Lund Area (WHILA) study. Climacteric 11: 304‐314, 2008.
 28. Grady D , Herrington D , Bittner V , Blumenthal R , Davidson M , Hatky M , Hsia J , Hulley S , Herd S , Khan S , Newby LK , Waters D , Vittinghoff E , Wenger N . Cardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and estrogen/progesterone replacement study follow‐up (HERS II). J Am Med Assoc 288: 49‐57, 2002.
 29. Hammel HT . Neurones and temperature regulation. AMRL‐TR [Aerospace Medical Research Laboratory] 232: 1‐32, 1965.
 30. Hardy JD , DuBois E . Differences between men and women in their response to heat and cold. Proc Natl Acad Sci U S A 26: 389‐398, 1940.
 31. Hardy JD , Milhorat T . Basal heat loss and production from women at temperatures from 23Cto 36C. Proc Soc Exp Biol Med 41: 94‐98, 1939.
 32. Hart EC , Charkoudian N , Miller VM . Sex, hormones and neuroeffector mechanisms. Acta Physiol (Oxf) 203: 155‐165, 2011.
 33. Hertig BA , Belding HS , Kraning KK , Batterton DL , Smith CR , Sargent F, II . Artificial acclimatization of women to heat. J Appl Physiol 18: 383‐386, 1963.
 34. Hertig BA , Sargent F, II . Acclimatization of women during work in hot environments. Fed Proc 22: 810‐813, 1963.
 35. Hirata K , Nagasaka T , Hirashita M , Takahata T , Nuriomura T . Effects of human menstrual cycle on thermoregulatory vasodilation during exercise. Euro J Appl Physiol 54: 559‐565, 1986.
 36. Hulley S , Furberg C , Barrett‐Connor E , Cauley J , Grady D , Haskell W , Knopp R , Lowery M , Satterfield S , Schrott H , Vittinghoff E , Hunninghake D . Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and estrogen/progesterone replacement study follow‐up (HERS II). J Am Med Assoc 288: 58‐66, 2002.
 37. Johnson JM , Kellogg DL, Jr . Thermoregulatory and thermal control in the human cutaneous circulation. Front Biosci (Schol Ed) 2: 825‐853, 2010.
 38. Kolka M , Stephenson L . Control of sweating during the human menstrual cycle. Eur J Appl Physiol 58: 890‐895, 1989.
 39. Kolka MA , Stephenson LA . Effect of luteal phase elevation in core temperature on forearm blood flow during exercise. J Appl Physiol 82: 1079‐1083, 1997.
 40. Kolka MA , Stephenson LA . Resetting the thermoregulatory set‐point by endogenous estradiol or progesterone in women. Ann N Y Acad Sci 813: 204‐206, 1997.
 41. Laughlin GA , Barrett‐Connor E . Sexual dimorphism in the influence of advanced aging on adrenal hormone levels: the Rancho Bernardo Study. J Clin Endocrinol Metab 85: 3561‐3568, 2000.
 42. Lovett C . The fight to establish the women's race. In: Olympic Marathon: A Centennial History of the Games' Most Storied Race. Praeger, 1997.
 43. Mason E . The basal metabolism of European women in South India and the effect of change of climate in European and South Indian women. J Nutri 8: 695, 1934.
 44. Mesch VR , Siseles NO , Maidana PN , Boero LE , Sayegh F , Prada M , Royer M , Schreier L , Benencia HJ , Berg GA . Androgens in relationship to cardiovascular risk factors in the menopausal transition. Climacteric 11: 509‐517, 2008.
 45. Mittelman‐Smith MA , Williams H , Krajewski‐Hall SJ , McMullen NT , Rance NE . Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. Proc Natl Acad Sci USA 109: 19846‐19851, 2012.
 46. Morrison SF , Nakamura K . Central neural pathways for thermoregulation. Front Biosci (Landmark Ed) 16: 74‐104, 2011.
 47. Nadel ER , Pandolf KB , Roberts MF , Stolwijk JA . Mechanisms of thermal acclimation to exercise and heat. J Appl Physiol 37: 515‐520, 1974.
 48. Nakayama T , Suzuki M , Ishizuka N . Action of progesterone on thermosensitive neurons. Nature 258: 80, 1975.
 49. Oberye JJL , Mannaerts BMJL , Huisman JAM , Timmer CJ . Pharmacokinetic and Pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers. Fertil Steril 72: 1001‐1005, 1999.
 50. Oberye JJL , Mannaerts BMJL , Huisman JAM , Timmer CJ . Pharmacokinetic and Pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part II. Dose‐proportionality and gonadotropin suppression after multiple doses of ganirelix in healthy female volunteers. Fertil Steril 72: 1006‐1012, 1999.
 51. Pergola PE , Kellogg DL, Jr , Johnson JM , Kosiba WA . Reflex control of active cutaneous vasodilation by skin temperature in humans. Am J Physiol 247 (Heart Circ Physiol. 26): H1979‐H1984, 1994.
 52. Prior J , Hitchcock C . Progesterone for hot flush and night sweat treatment – effectiveness for severe vasomotor symptoms and lack of withdrawal rebound. Gynecological Endocrinol 28: 7‐11, 2012.
 53. Reckelhoff JF , Granger JP . Role of androgens in mediating hypertension and renal injury. Clin Experimental Pharmacol Physiol 26: 127‐131, 1999.
 54. Roberts MF , Wenger CB , Stolwijk JA , Nadel ER . Skin blood flow and sweating changes following exercise training and heat acclimation. J Appl Physiol 43: 133‐137, 1977.
 55. Roesch DM , Keller‐Wood M . Progesterone rapidly reduces arterial blood pressure in ewes. Am J Physiol 272 (Heart Circulatory Physiol): H386‐H391, 1997.
 56. Rogers SM , Baker MA . Thermoregulation during exercise in women who are taking oral contraceptives. Eur J Appl Physiol 75: 34‐38, 1997.
 57. Rowell LB . Cardiovascular adjustments to thermal stress. In: Handbook of Physiology. The Cardiovascular System: Peripheral Circulation and Organ Blood Flow. Bethesda: American Physiological Society, 1983, pp. 967‐1023.
 58. Savage M , Brengelmann GL . Control of skin blood flow in the neutral zone of human thermoregulation. J Appl Physiol 80: 1249‐1257, 1996.
 59. Shapiro Y , Pandolf KB , Avellini BA , Pimental NA , Goldman RF . Physiological responses of men and women to humid and dry heat. J Appl Physiol 49: 1‐8, 1980.
 60. Silva NL , Boulant JA . Effects of testosterone, estradiol, and temperature on neurons in preoptic tissue slices. Am J Physiol 250 (Regulatory, Integrative, Comp. Physiol. 19): R625‐R632, 1986.
 61. Sokolnicki LA , Khosla S , Charkoudian N . Effects of testosterone and estradiol on cutaneous vasodilation during local warming in older men. Am J Physiol Endocrinol Metab 293: E1426‐1429, 2007.
 62. Speroff L , Glass RH , Kase NG . Steroid contraception. In: Clinical Gynecological Endocrinology and Infertility. Baltimore: Williams & Wilkins, 1999, pp. 873‐879.
 63. Stachenfeld NS , Keefe DL . Estrogen effects on osmotic regulation of AVP and fluid balance. Am J Physiol Endocrinol Metab. 283: E711‐E721, 2002.
 64. Stachenfeld NS , Silva C , Keefe DL . Estrogen modifies the temperature effects of progesterone. J Appl Physiol 88: 1643‐1649, 2000.
 65. Stachenfeld NS , Taylor HS . Sex hormone effects on body fluid and sodium regulation in women with and without exercise‐associated hyponatremia. J Appl Physiol 107: 864‐872, 2009.
 66. Stachenfeld NS , Yeckel CW , Taylor HS . Greater exercise sweating in obese women with polycystic ovary syndrome compared with obese controls. Med Sci Sports Exerc 42: 1660‐1668, 2010.
 67. Stephenson LA , Kolka MA . Esophageal temperature threshold for sweating decreases before ovulation in premenopausal women. J Appl Physiol 86: 22‐28, 1999.
 68. Stephenson LA , Kolka MA . Menstrual cycle phase and time of day alter reference signal controlling arm blood flow and sweating. Am J Physiol 249 (Regulatory Integrative Comp. Physiol. 18): R186‐R191, 1985.
 69. Stephenson LA , Kolka MA . Thermoregulation in women. In: Holloszy JO , editor. Exercise and Sports Science Reviews. Philadelphia: Williams and Wilkins, 1993, pp. 231‐262.
 70. Vega Orozco A , Daneri C , Anesetti G , Cabrera R , Sosa Z , Rastrilla AM . Involvement of the oestrogenic receptors in superior mesenteric ganglion on the ovarian steroidogenesis in rat. Reproduction 143: 183‐193, 2012.
 71. Weinman KP , Slabochova Z , Bernauer EM , Morimoto T , Sargent F, II . Reactions of men and women to repeated exposure to humid heat. J Appl Physiol 22: 533‐538, 1967.
 72. Wenner MM , Taylor HS , Stachenfeld NS . Progesterone enhances adrenergic control of skin blood flow in women with high but not low orthostatic tolerance. J. Physiol 589.4: 975‐986, 2011.
 73. WHO. What do we mean by “sex” and “gender”?: World Health Organization, 2012.
 74. Wyndham CH , Morrison JF , Williams CG . Heat reactions of male and female caucasians. J Appl Physiol 20: 357‐364, 1965.
 75. Yesalis CE , Barsukiewicz CK , Kopstein AN , Bahrke MS . Trends in anabolic‐androgenic steroid use among adolescents. Arch Pediatr Adolesc Med 151: 1197‐1206, 1997.

Related Articles:

Sex Differences

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Nisha Charkoudian, Nina S. Stachenfeld. Reproductive Hormone Influences on Thermoregulation in Women. Compr Physiol 2014, 4: 793-804. doi: 10.1002/cphy.c130029